Gene Regulation Is Necessary ~42 000 genes exist that code for
proteins in humans, but not all proteins are required By switching
genes off when they are not needed, cells can prevent resources
from being wasted. The ability to switch genes on an off is
naturally selected
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A typical human cell normally expresses about 3% to 5% of its
genes at any given time. Cancer results from genes that do not turn
off properly. Cancer cells have lost their ability to regulate
mitosis, resulting in uncontrolled cell division.
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Gene expression in eukaryotes is controlled by a variety of
mechanisms that range from those that prevent transcription to
those that prevent expression after the protein has been produced.
The various mechanisms can be placed into one of these four
categories: transcriptional, posttranscriptional, translational,
and posttranslational.
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Transcriptional prevent mRNA from being synthesized Ex: Barr
bodies in females are inactive because tightly wound
Post-transcriptional Regulate mRNA after it is produced Ex: a
single mRNA can code for 3 proteins, depending on which introns are
removed
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Translational Prevent protein synthesis Proteins may bind to
regions of the mRNA strand preventing the ribosomes from
translating it. Post-translational Prevent the protein from
becoming functional Ex: Proteins are often not fully functional
after translation. Proinsulin is a precursor to insulin. It needs
to be cut into 2 polypeptide chains and have 30 amino acids
removed.
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Prokaryotes Much of our understanding of gene control comes
from studies of prokaryotes.prokaryotes Prokaryotes have two levels
of gene control. Transcriptional and translational.
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Operons Operons are groups of genes that function to produce
proteins needed by the cell. Prokaryotic cells use operons to
regulate genes and their respective proteins.
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Operons are made up of: Structural Genes code for the proteins
needed. Ex: the proteins needed to breakdown sugar Promoter are
where RNA polymerase binds to the DNA (Lots of A-T base pairs!)
Operator a short sequence of bases between structural genes and a
promoter.
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The lac operon Lactose is a sugar found in milk. If lactose is
present, E. coli (the common intestinal bacterium) needs to produce
the necessary enzymes to digest it. Three different enzymes are
needed.
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In the diagram genes A, B, and C represent the genes whose
products are necessary to digest lactose. In the normal condition,
the genes do not function because a repressor protein is active and
bound to the DNA preventing transcription. When the repressor
protein is bound to the DNA, RNA polymerase cannot bind to the DNA.
The protein must be removed before the genes can be
transcribed.
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Lac operon with repressor (no transcription)
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Below: Lactose binds with the repressor protein inactivating
it.
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Transcription!
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Lac operon The lac operon is an example of an inducible operon
because the structural genes are normally inactive. They are
activated when lactose is present.
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The trp operon Repressible operons are the opposite of
inducible operons. Transcription occurs continuously and the
repressor protein must be activated to stop transcription.
Tryptophan is an amino acid needed by E. coli and the genes that
code for proteins that produce tryptophan are continuously
transcribed as shown below.
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However, if tryptophan is present in the environment, E. coli
does not need to synthesize it and the tryptophan-synthesizing
genes should be turned off. This occurs when tryptophan binds with
the repressor protein, activating it. Unlike the repressor
discussed with the lac operon, this repressor will not bind to the
DNA unless it is activated by binding with tryptophan. Tryptophan
is therefore a co-repressor.
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The trp operon is an example of a repressible operon because
the structural genes are active and are inactivated when tryptophan
is present.
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Negative and Positive Control The trp and lac operons discussed
above are examples of negative control because a repressor blocks
transcription. In one case (lac operon) the repressor is active and
prevents transcription. In the other case (trp) the repressor is
inactive and must be activated to prevent transcription.
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Positive control mechanisms require the presence of an
activator protein before RNA polymerase will attach. The activator
protein itself must be bound to an inducer molecule before it
attaches to mRNA.
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Genes which code for enzymes necessary for the digestion of
maltose are regulated by this mechanism. Maltose acts as the
inducer, binding to an activator and then to DNA. The activator
bound to DNA stimulates the binding of RNA polymerase.
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Methylation The attachment of a methyl group to histone
proteins can promote or inhibit transcription (by either causing
the DNA to unravel from the nucleosome or stay tightly bonded to
the nucleosome). If the methyl group is attached directly to DNA,
transcription will be inhibited because RNA polymerase cannot
attach.
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Methylation of Cytosine
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Methylation of a Nucleosome
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Methylation The amount of DNA methylation varies during a
lifetime and is affected by environmental factors. Identical twins
will have identical DNA but will have different levels of
methylation because they have different experiences. Differences in
the expressed genes is why identical twins may not look or act
exactly the same.
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Epigenetics Epigenetics is the study of cellular and
physiological traits that are NOT caused by changes in the DNA
sequence. This done via chemical modifications (such as
methylation, phosphorylation, or acetylation) and are called
epigenetic tags. Scientific evidence shows that not only does the
environment effect the expression of genes, but that epigenetic
factors may be heritable (passed on to the next generation).
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Different cells have their own methylation pattern so that a
unique set of proteins will be produced in order for that cell to
perform its function.
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During cell division, the methylation pattern will be passed
over to the daughter cell. In other words, the environment is
affecting inheritance. Sperm and eggs develop from cells with
epigenetic tags. When a sperm and egg cell meet to form a zygote,
the epigenome (the sum of all the epigenetic tags) are removed
through a process called reprogramming.
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About 1% of the epigenome is not erased and is passed on to the
next generation. This is called imprinting. Ex: A pregnant mother
may develop gestational diabetes (temporary diabetes while she is
pregnant). As a result, high levels of glucose in the fetus can
trigger epigenetic changes to the fetus DNA giving the child an
increased chance of developing diabetes itself.
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Data Base Question: Changes in Methylation Pattern with age in
Identical Twins
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One study compared the methylation patterns of 3-year olds
identical twins with 50 year old identical twins Methylation
patterns were dyed red on one chromosome for own twin and dyed
grene for the other twin on the same chromsomes. The result would
be a yellow colour if the patterns were the same. Differences in
patterns on the two chromosomes result in green and red patches.
This was done for 4 pairs of chromsomes.
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1. Explain the reason for the yellow colouration if the
methylation pattern is the same in the 2 twins. 2. Identify the
chromosome with the least changes as the twins age.
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3. Identify the chromosomes with the most changes as the twins
age. 4. Explain how these differences could arise 5. Predict with a
reason whether identical twins will become more or less similar to
each other in their characteristics as they grow older.